Employing an orthotopic model to study the role of epithelial-mesenchymal transition in bladder cancer metastasis.

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Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_62307F91C3C7
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Employing an orthotopic model to study the role of epithelial-mesenchymal transition in bladder cancer metastasis.
Journal
Oncotarget
Author(s)
Roth B., Jayaratna I., Sundi D., Cheng T., Melquist J., Choi W., Porten S., Nitti G., Navai N., Wszolek M., Guo C., Czerniak B., McConkey D., Dinney C.
ISSN
1949-2553 (Electronic)
ISSN-L
1949-2553
Publication state
Published
Issued date
23/05/2017
Peer-reviewed
Oui
Volume
8
Number
21
Pages
34205-34222
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
Epithelial-to-mesenchymal transition (EMT) has been implicated in the progression of bladder cancer. To study its contribution to bladder cancer metastasis, we established new xenograft models derived from human bladder cancer cell lines utilizing an orthotopic "recycling" technique that allowed us to isolate and examine the primary tumor and its corresponding circulating tumor cells (CTC's) and metastatic lesions. Using whole genome mRNA expression profiling, we found that a reversible epithelial-to-mesenchymal transition (EMT) characterized by TGFβ pathway activation and SNAIL expression was associated with the accumulation of CTCs. Finally, we observed that conditional silencing of SNAIL completely blocked CTC production and regional/distant metastasis. Using this unique bladder cancer xenograft model, we conclude that metastasis is dependent on a reversible EMT mediated by SNAIL.
Keywords
Animals, Cell Line, Tumor, Disease Models, Animal, Disease Progression, Epithelial-Mesenchymal Transition, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Humans, Neoplasm Metastasis, Neoplastic Cells, Circulating/metabolism, Neoplastic Cells, Circulating/pathology, Signal Transduction/drug effects, Snail Family Transcription Factors/genetics, Snail Family Transcription Factors/metabolism, Transforming Growth Factor beta/genetics, Transforming Growth Factor beta/metabolism, Urinary Bladder Neoplasms/genetics, Urinary Bladder Neoplasms/metabolism, Urinary Bladder Neoplasms/pathology, Whole Genome Sequencing, SNAIL, bladder cancer, circulating tumor cells, metastasis, orthotopic xenografts
Pubmed
Web of science
Open Access
Yes
Create date
08/01/2021 20:10
Last modification date
30/04/2021 7:11
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